This section provides background information related to the present disclosure which is not necessarily prior art.
PTT is the time delay for the energy wave to travel between two sites in the arteries. According to the Bramwell-Hill equation, PTT varies with the arterial compliance (i.e., PTT=√(LC), where L is the arterial inertance and C is the arterial compliance). PTT indeed decreases as the arteries stiffen with aging and disease. Further, PTT often shows a tight relationship with BP. The physiologic mechanism for this relationship is well understood. The arterial compliance decreases as BP increases, because collagen fibers are slack and do not apply tension until the arterial wall is stretched. PTT, in turn, decreases due to the Bramwell-Hill equation. While changes in vasomotor tone can also acutely modulate the arterial compliance, this effect is less of a factor in the aorta wherein smooth muscle is relatively sparse.
PTT can be estimated simply from the relative timing between proximal and distal waveforms indicative of the arterial pulse. Hence, PTT has (a) proven to be a convenient marker of arterial stiffness and (b) could conceivably permit continuous, non-invasive, and cuff-less BP monitoring in the acute setting and even over longer time periods (e.g., months to a few years) as the impact of aging and disease on the arteries are slow processes.
The conventional PTT estimation technique is to detect the foot-to-foot time delay between the proximal and distal waveforms. The premise is that arterial wave reflection interference is negligible during late diastole and early systole when the waveform feet occur. By contrast, the reflected wave is often prominent by late systole. So, the peak-to-peak time-delay between the two waveforms typically does not provide a useful PTT estimate. Hence, by virtue of being estimated at the waveform feet, conventionally estimated PTT is precisely a marker of arterial stiffness at the level of diastolic BP and generally correlates best with diastolic BP.
However, wave reflection interference may not always be negligible at the waveform feet, particularly as heart rate changes and peripheral resistance increases. Just as important, since the foot-to-foot detection technique restricts its analysis to one pair of waveform samples, it is not robust to motion and other common artifact in the waveforms. Hence, this technique yields imperfect PTT estimates. Even seemingly small errors are problematic, as PTT itself is small. Compounding matters, BP changes perturb PTT relatively little. As a result, plots of diastolic BP versus foot-to-foot PTT often show significant scatter about the line of best fit. This scatter obviously limits the ability of PTT to track BP.
Several techniques have been proposed to improve the estimation of PTT from the same waveforms. These techniques have been shown or could reduce the scatter in BP versus PTT plots.
Some of the techniques analyze multiple systolic samples of the waveforms to obtain a PTT estimate at a BP level somewhere between diastolic and mean BP (rather than at diastolic BP). One such technique fits a line through the early systolic samples of each waveform and then finds the time of its intersection with the horizontal line passing through the minimum BP to establish PTT. Another technique fits a hyperbolic tangent model to the entire systolic upstroke of at least one of the waveforms and then uses the time of the model inflection point(s) to arrive at PTT. A third technique effectively averages multiple time delays taken from the early to mid-systolic samples of the two waveforms to determine PTT. By analyzing additional waveform samples, these techniques are more robust to artifact. However, wave reflection interference becomes a greater factor as the cardiac cycle progresses.
Other techniques analyze the entire waveforms to arrive at a PTT estimate at likely mean BP. One such technique represents the relationship between the proximal and distal waveforms with a linear black-box (i.e., not physically based) model that assumes arterial compliance is independent of BP. Then, the impulse response that optimally couples the proximal waveform to the distal waveform is identified. Finally, the time delay of the impulse response is detected as the PTT. Since the impulse response represents the distal arterial response to a very narrow pulse applied at the proximal artery at time zero, this PTT estimate is not corrupted by wave reflection. Another technique represents the relationship between the proximal and distal waveforms with a linear physical model that likewise assumes that the arterial compliance is independent of BP and accounts for wave reflection from the periphery, which is typically the dominant impedance mismatch site. Then, all parameters of the model, which include the true PTT (i.e., PTT in absence of wave reflection), are estimated by optimally coupling the waveforms. Hence, both of these linear model-based techniques provide an artifact robust estimate of the true PTT.
Although a number of PTT estimation techniques have been conceived, all yield one PTT estimate at a single BP level. It would be desirable to have a technique that is able to estimate PTT as a function of BP (e.g., PTT for each and every BP level in the cardiac cycle). Such a technique would have at least three important patient monitoring applications.
One application is improved monitoring of arterial stiffness. In particular, the desired technique could be used to correct PTT for BP and thereby afford more meaningful tracking of arterial stiffness over time within a subject or more meaningful comparisons of arterial stiffness amongst different subjects.
Another application is calibrating PTT (in units of sec) to BP (in units of mmHg). To achieve this calibration, a subject-specific curve that relates PTT to BP (i.e., PTT as a function of BP) is needed. The conventional approach for constructing the curve is to measure both PTT and BP in a subject during an experimental perturbation that varies BP over a significant range such as vasoactive drug infusions. (BP could then be subsequently measured in that subject from only PTT by invoking the calibration curve.) However, the need for an experimental perturbation makes this approach less practical. The desired technique would provide the requisite curve without the need for inducing an artificial BP change (i.e., a “perturbationless calibration” approach).
A third application is tracking systolic BP via PTT. All of the previous techniques estimate PTT at BP levels between diastolic and mean BP and are thus best suited to track these BP values. The desired technique would afford a PTT estimate at systolic BP and thereby better track this BP value.
The background description provided herein is for the purpose of generally presenting the context of the invention. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present invention.